For this week's 'Thoughts from the Centre' we're delighted to share an article written by a US colleague: Terri Cooper – PhD, Principal, Federal Health Sector Leader, Deloitte Consulting LLP. Terri's 'My Take' discusses the challenges surrounding precision medicine and how recent trends are helping to unlock its potential.

Twenty-six years ago, researchers announced they had discovered the gene that causes cystic fibrosis (CF).1 Just three years ago, the US Food and Drug Administration (FDA) approved Ivacaftor (Kalydeco"), the first drug to target the underlying cause of CF: a faulty gene and its protein product. KalydecoTM is now approved for use in about 10 percent of patients who have particular genetic mutations. Though there is more work to be done to develop targeted therapies for patients with CF, the discovery of the gene and the decades-long quest for a targeted, effective treatment is a precision medicine success story.

Some diseases like CF and Huntington's disease stem from an error in a single gene. Unfortunately, many other, more common conditions (e.g., depression, autism and schizophrenia) likely result from the interaction of several genes and other factors. These can take years to identify. And even in the case of CF, multiple therapies may need to be developed to target different mutations. As another example, because cancers are caused by multiple mutations, it has long been recognized that it is not a disease that can be treated with a single therapy. Even cancers of the same tissue or organ vary significantly in their molecular details and have different responses to treatments.

Precision medicine offers the potential for more targeted therapies – targeting treatment to positively responding patients – and reducing adverse events. A recent report from the Tufts Center for the Study of Drug Development shows that investment in precision medicine has nearly doubled in the last five years.2Despite this growth in investment, we would be remiss to forget that targeted treatments still have to go through the rigorous and costly research and development process. And because the treatments may only be used for a small subset of patients, the return on investment is potentially reduced. It is both in spite of and because of these challenges that momentum around precision medicine is gathering like never before.

The President announced the Precision Medicine initiative in January, and funding for it is included in the President's Budget. The 21st Century Cures Act, which includes a provision around precision medicine as well as many other ideas to spur biomedical innovation, just passed the House of Representatives this month. Finally, last month, the National Cancer Institute (NCI) launched its "precision cancer" effort (see the June 9, 2015 Health Care Current) and the American Society of Clinical Oncology (ASCO) announced the Targeted Agent and Profiling Utilization Registry.

These initiatives are exciting to track, but both the Tufts report and a recent Deloitte report, "In the face of uncertainty: A challenging future for biopharmaceutical innovation," explain that there are still challenges to overcome in biopharma innovation. Scientific uncertainty and uncertainty around the regulatory and insurance coverage landscape continue to hinder innovation. Companies face challenges on the scientific front in the areas of biomarker identification and diagnostic test development. The report, "The current and future state of companion diagnostics," discusses the challenge around aligning incentives of the multiple stakeholders in the area of companion diagnostics.3 Regulators and payers want to see clear evidence of safety and efficacy. With the health care system transitioning toward value-based care, providers want to select a therapy based on diagnostic testing that compares similar therapeutics against one another. Drug developers want to see compelling economic incentives for the continued investment of time and money.

Companion diagnostics offers solutions to some of these challenges: Regulators see the potential for more directed regulatory submissions with fewer adverse events based on targeted therapies, while payers see the potential for fewer unnecessary treatments. Drug developers can achieve faster time to market with less expensive clinical trials for drugs with significant revenue potential. The uptake of targeted therapies, such as Herceptin® (trastuzumab) and Gleevec® (imatinib mesylate) which require testing with companion diagnostics before they can be prescribed, demonstrates the rapid evolution of companion diagnostics and the potential that some the above-mentioned challenges can be overcome.

I am encouraged by the momentum precision medicine is gaining. Dr. Francis Collins, Director of the National Institutes of Health, remarked at the annual Biotechnology Innovation Organization (BIO) International Convention recently that medical knowledge is far outpacing treatment gain, but that the Precision Medicine Initiative will greatly enhance our ability to take precision medicine from a promise to a reality. What is most exciting to me is the collaborative ecosystem that is emerging from these announcements. Examples like the NCI's precision cancer effort and ASCO's initiative both illustrate what can happen when the different stakeholders come together under the shared goal of getting the right treatment to the right patient at the right time. In the NCI example, the Molecular Analysis for Therapy Choice (MATCH) trial is currently enrolling thousands of patients with intractable cancers in 2,400 clinics around the country. Ten pharmaceutical companies are providing more than 20 drugs – some that are currently on the market and others that are still in development – to be tested on different gene mutations during the first few months of the trial. ASCO's Targeted Agent and Profiling Utilization Registry will collect real-world evidence on the outcomes of patients with advanced cancers who receive molecularly targeted drugs for uses not approved by the FDA.

Both of these large initiatives require a high level of coordination between the clinical trial networks, the pharmaceutical companies providing the drugs and the patient advocates who were engaged in the development of the trial and who will help oversee the protocols and other aspects of the study. Learnings from these initiatives could help demonstrate the power of informatics, connectivity and collaboration to spur biomedical innovation.

Currently there are around 7,000 known rare diseases. We have treatments for around 500 of them. In many ways, we are just setting out on the precision medicine path. If we can keep up this momentum, we may be well-positioned to make more ground-breaking discoveries that lead to many more cures.

Footnotes

1. http://www.cff.org/research/

2. Personalized Medicine Coalition and PhRMA, "Biopharmaceutical Companies' Personalized Medicine Research Yields Innovative Treatments for Patients," 2015: https://www.genomeweb.com/sites/default/files/public/downloads/news/pmc-phrma-personalized-medicine-investment.pdf

3. The FDA definition of companion diagnostic: A companion diagnostic device can be an in vitro diagnostic device or an imaging tool that provides information that is essential for the safe and effective use of a corresponding therapeutic product. The use of an in vitro diagnostic companion device with a particular therapeutic product is stipulated in the instructions for use in the labeling of both the device and the corresponding therapeutic product, as well as in the labeling of any generic equivalents and biosimilar equivalents of the therapeutic product.

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